A novel and highly selective conversion of alcohols, thiols, and silyl ethers to azides using the triphenylphosphine/2,3-dichloro-5,6- dicyanobenzoquinone(DDQ)/n-Bu4NN3 system

Article abstract of DOI:10.1016/j.tetlet.2004.02.141

Alcohols, thiols, and silyl ethers are converted into alkyl azides in good to excellent yields by treatment with PPh₃/DDQ/n-Bu ₄NN₃ in CH₂Cl₂ at room temperature. The method is highly selective for 1°

Full text of DOI:10.1016/j.tetlet.2004.02.141

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3291–3294
A novel and highly selective conversion of alcohols, thiols, and
silyl ethers to azides using the triphenylphosphine/2,3-dichloro-
5
,6-dicyanobenzoquinone(DDQ)/n-Bu NN system
4
3
*
*
Nasser Iranpoor, Habib Firouzabadi, Batool Akhlaghinia and Najmeh Nowrouzi
Department of Chemistry, Shiraz University, Shiraz 71454, Iran
Received 18 November 2003; revised 9 February 2004; accepted 20 February 2004
Abstract—Alcohols, thiols, and silyl ethers are converted into alkyl azides in good to excellent yields by treatment with PPh
n-Bu NN in CH Cl
at room temperature. The method is highly selective for 1° alcohols in the presence of 2° and 3° ones, and also
thiols and silyl ethers.
3
/DDQ/
4
3
2
2
Ó 2004 Elsevier Ltd. All rights reserved.
1
Azides are important functional groups in organic
synthesis for many purposes and have been extensively
used for the introduction of amino groups and con-
In continuation of our recent work on the use of TPP/
DDQ/nucleophile, for the preparation of alkyl halides,
and nitriles, we report the successful preparation of
primary, secondary, tertiary, and cycloalkyl azides from
alcohols, thiols, and trimethylsilyl ethers under mild
11
2
struction of heterocycles. Aliphatic azides are usually
prepared by nucleophilic substitution of the corre-
sponding halides or sulfonates by azide ion. Due to
the advantageous and attractive strategy of the direct
synthesis of azides from alcohols, some limited methods
have been developed. Along this line, methods based
on Mitsunobu conditions are widely applied. These
methods utilize reagents such as hydrazoic acid, diphen-
ylphosphoryl azide, the bispyridine complex of zinc
3
;4
reaction conditions using the TPP/DDQ/n-Bu NN3
4
system in high to excellent yields (Scheme 1).
The use of diethyl azodicarboxylate (DEAD) in Mits-
unobu reactions as an expensive reagent, which easily
explodes on heating and the use of HN as the source of
3
nucleophile are the two main problems for utilizing this
method for the conversion of alcohols to alkyl azides.
5
–7
azide or the tetrabromocyclohexadienone/Ph P system
3
as the azide source/nucleophilic component. The use of
8
NaN
3
in the presence of excess BF
3
–Et
2
O at 80–90 °C
In order to reduce the problems encountered in this
conversion and to provide a safer and simpler method,
was reported to be effective for the conversion of allylic
and benzylic alcohols to azides. The conversion of
activated alcohols to azides by the use of diphenyl
we decided to use n-Bu
ion instead of HN
4
NN
3
as the source of the azide
3
and studied the possibility
9
phosphorazidate (DPPA) and DBU and the use of
of replacing diethyl azodicarboxylate (DEAD) with
other electron-deficient reagents such as 2,3-dichloro-
5,6-dicyanobenzoquinone (DDQ), 2,3,5,6-tetrachlo-
robenzoquinone (p-chloranile), tetraphenylcyclopenta-
dienone (tetracyclone), tetracyanoethylene (TCNE),
10
bis(p-nitrophenyl) phosphorazidate have also been
reported. The latter method cannot be applied for cyclic
alcohols, for example, cyclohexanol does not react with
this reagent even after 24 h reflux in toluene.
diethyl
acetylenedicarboxylate
(DEACD),
and
Keywords: Triphenylphosphine (TPP); 2,3-Dichloro-5,6-dicyano-
benzoquinone (DDQ); Azide; Alcohol; Thiol; Trimethylsilylether.
Ph P/DDQ/n-Bu NN
3
3
4
RY
RN
3
CH Cl , rt
2
2
*
Corresponding authors. Tel.: +98-711-2287600; fax: +98-711-2280-
26; e-mail addresses: iranpoor@chem.susc.ac.ir; firouzabadi@chem.
susc.ac.ir
9
Y = OH, SH, OSiMe
3
o
o
o
R = 1 , 2 and 3 alkyl
On leave from Department of Chemistry, Dameghan University of
Basic Sciences, Dameghan, Iran.
Scheme 1.
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.141

3292
N. Iranpoor et al. /Tetrahedron Letters 45 (2004) 3291–3294
Table 1. The conversion of benzyl alcohol to benzyl azide using
n-Bu NN in the presence of Ph P and different reagents in dichloro-
methane at room temperature
was found to be the most suitable and efficient reagent
system for this conversion. The use of the other reagent
systems (Table 1, entries 1, 3–7) was not successful.
4
3
3
a
Entry Mixed reagent
Time
Conversion (%)
The optimized stoichiometric ratios of ROH/Ph
DDQ/n-Bu NN for the conversion of benzyl alcohol
3
P/
1
2
3
4
5
6
7
Ph
3
3
3
3
3
3
3
P/DEAD
P/DDQ
24 h
10
100
90
0
Ph
Ph
Ph
Ph
Ph
Ph
Immediately
24 h
24 h
4
3
P/p-chloranile
P/tetracyclone
P/TCNE
to benzyl azide were found to be 1/1.5/2/2 and the
reaction was performed in CH Cl at room temperature.
The amount of DDQ should be higher than Ph P
2
2
24 h
24 h
0
3
P/DEACD
P/PTAD
0
3
otherwise the Ph P can convert the alkyl azide to an
iminophosphorane, which reduces the yield of the
reaction.
24 h
0
a
GC yield using internal standard.
phenyl-1,2,4-triazoline-3,5-dione (PTAD) in conjunc-
tion with Ph P (TPP). In a set of experiments, we
studied the conversions of benzyl alcohol to benzyl azide
We then applied the optimized conditions to the con-
version of different alcohols into the corresponding alkyl
azides. The results obtained are shown in Table 2. These
show the general applicability of the method for the
conversion of primary, secondary, and tertiary alcohols
to alkyl azides.
3
with n-Bu NN in the presence of Ph P and the above-
4
3
3
mentioned reagents. The results of this study are shown
in Table 1. According to the results obtained, Ph P/DDQ
3
Table 2. Conversion of alcohols, thiols, and silyl ethers into alkyl azides
a
Entry
ROH
Time
3 h
Conversion (%)
Isolated yield (%)
1
2
OH
100
80
––
75
OH
2 h
3
4
10 h
20 h
80
90
78
88
OH
OH
b
5
6
7
24 h
70
100
100
100
65
95
95
96
OH
OH
2 h
OH
5 min
OH
8
9
Immediately
OH
40 min
100
100
97
94
Cl
OH
1
1
0
1
Immediately
H CO
3
OH
10 min
24 h
100
70
90
68
OH
SH
1
2
1
1
3
4
SH
24 h
24 h
90
90
85
84
SH
15
5 h
100
95

N. Iranpoor et al. /Tetrahedron Letters 45 (2004) 3291–3294
3293
Table 2 (continued)
a
Entry
ROH
Time
5 h
Conversion (%)
Isolated yield (%)
16
17
18
OSiMe3
100
93
73
92
10 h
80
OSiMe3
OSiMe3
5 min
100
a
GC yield using internal standard.
Reflux conditions.
b
We also applied this method successfully for the con-
version of thiols and silyl ethers into the corresponding
azides (Table 2, entries 13–18).
3
Table 3. Selective reactions of different binary mixtures with Ph P/
a
4 3
DDQ/n-Bu NN
b
Entry Binary mixture
Time (min)
Conversion
%)
(
This method was found to be highly selective for pri-
mary alcohols. In a binary mixture of 2-phenylethanol
and 2-octanol, the primary alcohol was completely
converted into its azide, while only a 5% conversion was
observed for the secondary alcohol (Table 3, entry 1).
Excellent selectivity was also observed for the conver-
sion of 1° and 2° alcohols in the presence of a 3° alcohol
(Table 3, entries 2 and 3). Similarly, this method showed
excellent selectivity for the conversion of 1° and 2°
alcohols into the corresponding azides in the presence
of trimethylsilyl ethers (Table 3, entries 4 and 5). High
selectivity for the conversion of alcohols in the presence
of thiols was also achieved with this method (Table 3,
entry 6). This method is also selective for the conversion
of 1° silyl ethers into the corresponding alkyl azides in
the presence of a 2° silyl ether (Table 3, entry 7).
OH
1
00
5
1
10
OH
OH
1
00
0
2
5
OH
OH
100
0
3
15
OH
In conclusion, replacement of DEAD with DDQ as a
safe and easily available reagent and HN3 with
4 3 3
n-Bu NN in combination with Ph P provides a simple,
OH
1
00
0
novel, and general method for the conversion of alco-
hols, thiols, and trimethylsilylethers into the corre-
sponding azides. In addition, this method shows
excellent selectivity for alcohols in the presence of
trimethylsilyl ethers and thiols as well as between
structurally different alcohols.
4
5
Immediately
OSiMe3
OH
100
0
Typical procedure for the conversion of benzyl alcohol to
benzyl azide in dichloromethane: To a flask containing a
stirred mixture of Ph P (1.5 mmol, 0.393 g) and DDQ
3
(2 mmol, 0.454 g) in dry dichloromethane (5–7 mL), was
10
OSiMe3
added tetra-n-butylammonium azide (2 mmol, 0.568 g)
at room temperature. Benzyl alcohol (1mmol, 0.1mL)
was then added to the reaction mixture. GC analysis
showed the immediate completion of the reaction. The
solvent was evaporated under reduced pressure. Column
chromatography of the crude residue on silica gel using
n-hexane as an eluent gave benzyl azide in 96% yield (bp
OH
SH
1
00
6
7
5
3
OSiMe3
12
73 °C, 11 mmHg. Lit. 108 ° C, 23 mmHg).
1
00
15
5
Acknowledgements
OSiMe3
a
We gratefully acknowledge the support of this study by
Shiraz University Research Council and Iran TWAS
Chapter Based at ISMO.
The stoichiometry of the binary mixture/Ph
/1/1.5/2/2.
3
P/DDQ/n-Bu4NN
3
was
1
GC yield using internal standard.
b

3294
N. Iranpoor et al. /Tetrahedron Letters 45 (2004) 3291–3294
8. Sampath, H. M.; Subba Reddy, B. V.; Anjaneyulu, S.;
References and notes
Yadav, J. S. Tetrahedron Lett. 1998, 39, 7385–7388.
. Thompson, A. S.; Humphrey, G. R.; DeMarco, A. H.;
Mathre, D. J.; Grabowski, E. J. J. J. Org. Chem. 1993, 58,
9
1
2
3
. Scriven, E. F. V.; Turnbull, K. Chem. Rev. 1988, 88, 297–
68.
. Sheradsky, T. In The Chemistry of the Azido Group; Patai,
S., Ed.; Interscience: New York, 1971; p 331.
. Biffin, M. E. C.; Miller, J.; Paul, D. B. In The Chemistry of
the Azido Group; Patai, S., Ed.; Interscience: New York,
3
5
886–5888.
0. Mizuno, M.; Shioiri, T. Chem. Commun. 1997, 2165–
166.
1
1
2
1. (a) Iranpoor, N.; Firouzabadi, H.; Aghapour, Gh.; Vaes
Zadeh, A. R. Tetrahedron 2002, 58, 8689–8693; (b)
Iranapoor, N.; Firouzabadi, H.; Akhlaghinia, B.; Now-
rouzi, N. J. Org. Chem., in press.
1971; p 5.
4. Alvarez, S. G.; Alvarez, M. T. Synthesis 1997, 413–414.
5. Hughes, D. L. Org. React. 1992, 42, 335–337.
6. Hughes, D. L. Org. Prep. Proced. Int. 1996, 28, 127.
7. Saito, A.; Saito, K.; Tanaka, A.; Oritani, T. Tetrahedron
Lett. 1997, 38, 3955–3958.
1
2. Lide, D. R. Handbook of Chemistry and Physics, 80th ed.;
1
999–2000.